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Diabetes mellitus
Related articles
Types of diabetes
Prediabetes:
   • Impaired fasting glycaemia
   • Impaired glucose tolerance
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes
Blood tests
Blood sugar
Glycosylated hemoglobin
Glucose tolerance test
Fructosamine
Diabetes management
Diabetic diet
Anti-diabetic drugs
Insulin therapy
Glossary of diabetes
Complications
Cardiovascular disease
Diabetic comas:
   • Diabetic hypoglycemia
   • Diabetic ketoacidosis
   • Nonketotic hyperosmolar
Diabetic myonecrosis
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy
Diabetes and pregnancy

Glycated hemoglobin (hemoglobin A1c, HbA1c, A1C, or Hb1c; sometimes also HbA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose. Glycation of hemoglobin has been associated with cardiovascular disease, nephropathy and retinopathy in diabetes mellitus. Monitoring the HbA1c in type-1 diabetic patients may improve treatment.[1]

Contents

History

Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column.[2] It was first characterized as a glycoprotein by Bookchin and Gallop in 1968.[3] Its increase in diabetes was first described in 1969 by Samuel Rahbar and coworkers[4] The reactions leading to its formation were characterized by Bunn and his co-workers in 1975.[5] The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.[6]

Underlying principle

In the normal 120-day life span of the red blood cell, glucose molecules react with hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycated hemoglobins are much higher than in healthy people.

Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell therefore reflects the average level of glucose to which the cell has been exposed during its life cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather shorter period of two to four weeks. [7]. The 2010 American Diabetes Association Standards of Medical Care in Diabetes added the A1c ≥ 6.5% as another criteria for the diagnosis of diabetes.[8]

Measuring A1C

There are a number of techniques used to measure A1C.

Laboratories use :

Point of care (eg doctors surgery) devices use :

  • Immunoassay
  • Boronate Affinity Chromatography

In the United States, POC A1C tests are certified by the National Glycohemoglobin Standardization Program (NGSP) to standardise them against the results of the 1993 Diabetes Control and Complications Trial (DCCT).[9]

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Switch to IFCC units

The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) and International Diabetes Federation (IDF) have agreed that in the future HbA1c is to be reported in the International Federation of Clinical Chemistry (IFCC) units.[10] IFFC reporting was introduced in Europe except for the UK in 2003,[11] and the UK has as of 1st June 2009 introduced dual reporting[12] until 1st June 2011.[13]

Conversion between the units is by the following equation:[14] IFCC-HbA1c (mmol/mol) = [DCCT-HbA1c (%) - 2.15] × 10.929

DCCT- HbA1c IFCC-HbA1c
(%) (mmol/mol)
4.0 20
5.0 31
6.0 42
6.5 48
7.0 53
7.5 59
8.0 64
9.0 75
10.0 86

Interpretation of results

Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation among individuals. Two individuals with the same average blood sugar can have A1C values that differ by as much as 3 percentage points.[15] In general, the reference range (that found in healthy persons), is about 4%–5.9%.[16]

Higher levels of HbA1c are found in people with persistently elevated blood sugar, as in diabetes mellitus. While diabetic patient treatment goals vary, many include a target range of HbA1c values. A diabetic person with good glucose control has a HbA1c level that is close to or within the reference range. The International Diabetes Federation and American College of Endocrinology recommend HbA1c values below 6.5%, while American Diabetes Association recommends that the HbA1c be below 7.0% for most patients.[17] Recent results from large trials suggest that a target below 7% may be excessive: Below 7% the health benefits of reduced A1C become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of dangerous hypoglycemic episodes.[18] Practitioners need to consider an individual patient's health, their risk of hypoglycemia, and their specific health risks when setting a target A1C level. For example, patients at high risk of microvascular complications may gain further benefits from reducing A1C below 7%. Because patients are responsible for averting or responding to their own hypoglycemic episodes, the patient's input and the doctor's assessment of the patient's self-care skills are also important.

A high HbA1c represents poor glucose control. However, a 'good' HbA1c in a patient with diabetes can still be riddled with a history of recent hypoglycemia, or, alternatively, spikes of hyperglycemia. Regular blood glucose monitoring is still the best method for the analysis of overall vascular health with respect to blood sugar control. Often, patients with diabetes mellitus are scolded by their doctors for having an HbA1c which is too low, because a lower A1C would indicate a likelihood of frequent hypoglycemia in the recent past. This is often assessed with blood sugar data and receptions are typically mixed. A balance of long term health (hyperglycemia prevention) versus short term health (hypoglycemia prevention) is always a constant concern for both patients and their doctors. Doctors are especially sensitive about lower level HbA1c's with patients who regularly drive, this being a prime example of a short-term motivation for preventing hypoglycemia. Many diabetics have died behind the wheel as a result of a low blood sugar, especially for the reason that frequent hypoglycemia results in a higher tolerance (ideally the patient is seized with a feeling of panic, an increased heart rate, profuse sweating, etc.) for the condition and some patients may not even consciously realize their blood sugar has dropped to dangerous levels. In addition to acquired tolerance, the use of alcohol and certain drugs (marijuana, for example) can create moderately similar symptoms to those of hypoglycemia (especially when used in combination) and for this reason the patient may not realize he/she has developed hypoglycemia.

Persistent elevations in blood sugar (and therefore HbA1c) increase the risk for the long-term vascular complications of diabetes such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor wound healing.

Lower than expected levels of HbA1c can be seen in people with shortened red blood cell life span, such as with glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red blood cell death. Conversely, higher than expected levels can be seen in people with a longer red blood cell life span, such as with Vitamin B12 or folate deficiency.

The approximate mapping between HbA1c values and eAG (estimated Average Glucose) measurements is given by the following equation:[15]

eAG(mg/dl) = 28.7 × A1C − 46.7
eAG(mmol/l) = 1.59 × A1C − 2.59
Data in parentheses are 95% CIs
HbA1c eAG (estimated Average Glucose)
(%) (mmol/L) (mg/dL)
5 5.4 (4.2–6.7) 97 (76–120)
6 7.0 (5.5–8.5) 126 (100–152)
7 8.6 (6.8–10.3) 154 (123–185)
8 10.2 (8.1–12.1) 183 (147–217)
9 11.8 (9.4–13.9) 212 (170–249)
10 13.4 (10.7–15.7) 240 (193–282)
11 14.9 (12.0–17.5) 269 (217–314)
12 16.5 (13.3–19.3) 298 (240–347)

Indications and use

Glycated hemoglobin is recommended for both (a) checking blood sugar control in people who might be pre-diabetic and (b) monitoring blood sugar control in patients with more elevated levels, termed diabetes mellitus. There is a significant proportion of people who are unaware of their elevated HbA1c level before they have blood lab work.[19] For a single blood sample, it provides far more revealing information on glycemic behavior than a fasting blood sugar value. That being said, fasting blood sugar tests are crucial in making treatment decisions. The American Diabetes Association guidelines are similar to others in advising that the glycosylated hemoglobin test be performed at least two times a year in patients with diabetes who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients with diabetes whose therapy has changed or who are not meeting glycemic goals.[20]

Glycated hemoglobin measurement is not appropriate where there has been a change in diet or treatment within 6 weeks. Likewise the test assumes a normal red blood cell aging process and mix of hemoglobin subtypes (predominantly HbA in normal adults). Hence people with recent blood loss or hemolytic anemia, or genetic differences in the hemoglobin molecule (hemoglobinopathy) such as sickle-cell disease and other conditions are not suitable for this test.

Due to glycated hemoglobin's variability (as shown in the table above), additional measures should be checked in patients who are at or near recommended goals. People who have hemoglobin A1C values at 8.0% or less should be provided additional testing to determine if the HbA1c values are due to averaging out high blood glucose (hyperglycemia) with low blood glucose (hypoglycemia), or if the HbA1c is more reflective of an elevated blood glucose that does not vary much throughout the day. Devices such as continuous blood glucose monitoring allow people with diabetes to determine their blood glucose levels on a continuous basis, testing every few minutes, although they are not widely used and have only been FDA approved to be used for up to one week at the most. Another test that is useful in determining if HbA1c values are due to wide variations of blood glucose throughout the day is 1,5 Anhydroglucitol, also known as GlycoMark. GlycoMark reflects only the times that a person is experiencing hyperglycemia above 180mg/dL of glucose (glucosuria) over a two week period.

Concentrations of hemoglobin A1 (HbA1) are increased, both in diabetic patients and in patients with renal failure, when measured by ion-exchange chromatography. The thiobarbituric acid method (a chemical method specific for the detection of glycation), shows that patients with renal failure have values for glycated hemoglobin similar to those observed in normal subjects, suggesting that the high values in these patients are a result of binding of something other than glucose to hemoglobin.[21]

In autoimmune hemolytic anemia, concentrations of hemoglobin A1 (HbA1) is undetectable. Administration of prenidsolone (PSL) will allow the HbA1 to be detected. [22] The alternative fructosamine test may be used in these circumstances and it similarly reflects an average of blood glucose levels over the preceding 2 to 3 weeks.

All the major institutions like International Expert Committee Report, drawn from the International Diabetes Federation (IDF), the European Association for the Study of diabetes (EASD), and the American Diabetes Association (ADA), suggests the A1C level of 6.5% as a diagnostic level.[23] The Committee Report further states that when A1C testing cannot be done, the fasting and glucose tolerance tests be done.

Diagnosis of diabetes during pregnancy continues to require fasting and glucose tolerance measurements for gestational diabetes and not the glycated hemoglobin.

References

  1. ^ Larsen ML, Hørder M, Mogensen EF (1990). "Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus". N. Engl. J. Med. 323 (15): 1021–5. PMID 2215560.  
  2. ^ Huisman TH, Martis EA, Dozy A (1958). "Chromatography of hemoglobin types on carboxymethylcellulose". J. Lab. Clin. Med. 52 (2): 312–27. PMID 13564011.  
  3. ^ Bookchin RM, Gallop PM (1968). "Structure of hemoglobin A1c: nature of the N-terminal beta chain blocking group". Biochem. Biophys. Res. Commun. 32 (1): 86–93. doi:10.1016/0006-291X(68)90430-0. PMID 4874776.  
  4. ^ Rahbar S, Blumenfeld O, Ranney HM (1969). "Studies of an unusual hemoglobin in patients with diabetes mellitus". Biochem. Biophys. Res. Commun. 36 (5): 838–43. doi:10.1016/0006-291X(69)90685-8. PMID 5808299.  
  5. ^ Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975). "Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c". Biochem. Biophys. Res. Commun. 67 (1): 103–9. doi:10.1016/0006-291X(75)90289-2. PMID 1201013.  
  6. ^ Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976). "Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus". N. Engl. J. Med. 295 (8): 417–20. PMID 934240.  
  7. ^ "Hemoglobin A1c Fact Sheet". Michigan Diabetes Research & Training Center. http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm. Retrieved 2007-12-26.  
  8. ^ Executive Summary: Standards of Medical Care in Diabetes—2010: Current criteria for the diagnosis of diabetes. Diabetes Care January 2010 33:S4-S10; doi:10.2337/dc10-S004
  9. ^ Developing Point of care HbA1c tests for Diabetes monitoring, Barry Plant, Originally Published IVDT July/August 2008
  10. ^ Geistanger A, Arends S, Berding C, et al. (August 2008). "Statistical methods for monitoring the relationship between the IFCC reference measurement procedure for hemoglobin A1c and the designated comparison methods in the United States, Japan, and Sweden". Clin. Chem. 54 (8): 1379–85. doi:10.1373/clinchem.2008.103556. PMID 18539643.  
  11. ^ Manley S, John WG, Marshall S (July 2004). "Introduction of IFCC reference method for calibration of HbA: implications for clinical care". Diabet. Med. 21 (7): 673–6. doi:10.1111/j.1464-5491.2004.01311.x. PMID 15209757.  
  12. ^ "Standardisation of the reference method for the measurement of HbA1c to improve diabetes care" (PDF). The Association for Clinical Biochemistry and Diabetss UK. April 2008. http://www.acb.org.uk/docs/hba1c.pdf. Retrieved 2009-07-02.  
  13. ^ "All Change For HbA1c" (PDF). University Hospital of South Manchester. http://elearn-uhsm.co.uk/pathhandbook/Pathways_May_09.pdf. Retrieved 2009-07-02.  
  14. ^ "HbA1c Standardisation For Laboratory Professionals" (PDF). Diabetes UK. http://www.diabetes.org.uk/upload/Professionals/Key%20leaflets/53130HbA1cLableaflet.pdf. Retrieved 2009-07-02.  
  15. ^ a b Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ (2008). "Translating the A1C assay into estimated average glucose values.". Diabetes Care 31 (8): 1473–8. doi:10.2337/dc08-0545. PMID 18540046. PMC 2742903. http://care.diabetesjournals.org/content/31/8/1473.full.  
  16. ^ "Hemoglobin A1c Test". MedicineNet.com. http://www.medicinenet.com/hemoglobin_a1c_test/article.htm. Retrieved 2007-12-26.  
  17. ^ "Executive Summary: Standards of medical care in diabetes—2009". Diabetes Care 32: S6–S12. 2009. doi:10.2337/dc09-S006.  
  18. ^ Lehman R, Krumholz HM (2009). "Tight control of blood glucose in long standing type 2 diabetes". Brit Med J 338: b800. doi:10.1136/bmj.b800.  
  19. ^ Walid MS, Newman BF, Yelverton JC, Nutter JP, Ajjan M, Robinson JS Jr (2009). "Prevalence of previously unknown elevation of glycosylated hemoglobin (HbA1c) in spine surgery patients and impact on length of stay and total cost". J Hosp Med: NA. doi:10.1002/jhm.541. PMID 19753643.  
  20. ^ American Diabetes Association (2007). "Standards of medical care in diabetes--2007". Diabetes Care 30 (Suppl 1): S4–S41. doi:10.2337/dc07-S004. PMID 17192377.  
  21. ^ "Glycated Hemoglobin in Uremic Patients as Measured by Affinity and Ion-Exchange Chromatography". clinchem.com. http://www.clinchem.org/cgi/reprint/30/3/485.pdf. Retrieved 2009-08-31.  
  22. ^ "Undetectable Glycated Hemoglobin in Autoimmune Hemolytic Anemia". repository.oai.yamaguchi-u.ac.jp. http://repository.oai.yamaguchi-u.ac.jp/yunoca/A02/A020052000103.pdf. Retrieved 2009-08-31.  
  23. ^ The International Expert Committee (2009). "International expert committee report on the role of the A1C assay in the diagnosis of diabetes". Diabetes Care 32 (7): 1327–1334. doi:10.2337/dc09-9033. PMID 19502545.  

See also

External links


Diabetes mellitus
Related articles
Types of diabetes
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes
Prediabetes:
   • Impaired fasting glycaemia
   • Impaired glucose tolerance
Blood tests
Blood sugar
Glycosylated hemoglobin
Glucose tolerance test
Fructosamine
Disease management
Diabetes management:
   • Anti-diabetic drugs
   • Conventional insulinotherapy
   • Diabetic diet
   • Intensive insulinotherapy
Glossary of diabetes
Complications
Cardiovascular disease
Diabetic comas:
   • Diabetic hypoglycemia
   • Diabetic ketoacidosis
   • Nonketotic hyperosmolar
Diabetic myonecrosis
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy
Diabetes and pregnancy

Glycosylated (or glycated) hemoglobin (hemoglobin A1c, Hb1c , HbA1c, or A1C; sometimes also HgA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose. Glycosylation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes mellitus. Monitoring the HbA1c in type-1 diabetic patients may improve treatment.[1]

Contents

History

Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column.[2] It was first characterized as a glycoprotein by Bookchin and Gallop in 1968.[3] Its increase in diabetes was first described in 1969 by Samuel Rahbar and coworkers[4] The reactions leading to its formation were characterized by Bunn and his co-workers in 1975.[5] The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.[6]

Underlying principle

In the normal 120-day life span of the red blood cell, glucose molecules react with hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycated hemoglobins are much higher than in healthy people.

Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell therefore reflects the average level of glucose to which the cell has been exposed during its life cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather shorter period of two to four weeks.[7]

Measuring A1c

There are a number of techniques used to measure A1c.

Laboratories use :

  • high-performance liquid chromatography (HPLC)
  • Immunoassay

Point of care (eg doctors surgery) devices use :

  • Immunoassay
  • Boronate Affinity Chromatography

In the United States, POC A1c tests are certified by the National Glycohemoglobin Standardization Program (NGSP) to standardise them against the results of the 1993 Diabetes Control and Complications Trial (DCCT).[8]

Switch to IFCC units

The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) and International Diabetes Federation (IDF) have agreed that in future HbA1c is to be reported in the International Federation of Clinical Chemistry (IFCC) units.[9] IFFC reporting was introduced in Europe except for the UK in 2003,[10] and the UK has as of 1st June 2009 introduced dual reporting[11] until 1st June 2011.[12]

Conversion between the units is by the following equation:[13] IFCC-HbA1c (mmol/mol) = [DCCT-HbA1c (%) - 2.15] × 10.929

DCCT- HbA1c IFCC-HbA1c
(%) (mmol/mol)
4.0 20
5.0 31
6.0 42
6.5 48
7.0 53
7.5 59
8.0 64
9.0 75
10.0 86

Interpretation of results

Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation among individuals. Two individuals with the same average blood sugar can have A1C values that differ by as much as 1 percentage point.[14] In general, the reference range (that found in healthy persons), is about 4%–5.9%.[15]

Higher levels of Hb A1c are found in people with persistently elevated blood sugar, as in diabetes mellitus. While diabetic patient treatment goals vary, many include a target range of Hb A1c values. A diabetic person with good glucose control has a Hb A1c level that is close to or within the reference range. The International Diabetes Federation and American College of Endocrinology recommend Hb A1c values below 6.5%, while American Diabetes Association recommends that the Hb A1c be below 7.0% for most patients.[16] Recent results from large trials suggest that a target below 7% may be excessive: Below 7% the health benefits of reduced A1C become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of dangerous hypoglycemic episodes.[17] Practitioners need to consider an individual patient's health, their risk of hypoglycemia, and their specific health risks when setting a target A1C level. For example, patients at high risk of microvascular complications may gain further benefits from reducing A1C below 7%. Because patients are responsible for averting or responding to their own hypoglycemic episodes, the patient's input and the doctor's assessment of the patient's self-care skills are also important.

A high HbA1c represents poor glucose control. However, a 'good' HbA1c in a patient with diabetes can still be riddled with a history of recent hypoglycemia, or, alternatively, spikes of hyperglycemia. Regular blood glucose monitoring is still the best method for the analysis of overall vascular health with respect to blood sugar control. Often, patients with diabetes mellitus are scolded by their doctorsTemplate:Fact for having a HbA1c which is too low, because a lower A1c would indicate a likelihood of frequent hypoglycemia in the recent past. This is often assessed with blood sugar data and receptions are typically mixed. A balance of long term health (hyperglycemia prevention) versus short term health (hypoglycemia prevention) is always a constant concern for both patients and their doctors. Doctors are especially sensitive about lower level HbA1c's with patients who regularly drive, this being a prime example of a short-term motivation for preventing hypoglycemia. Many diabetics have died behind the wheel as a result of a low blood sugarTemplate:Fact, especially for the reason that frequent hypoglycemia results in a higher tolerance (ideally the patient is seized with a feeling of panic, an increased heart rate, profuse sweating, etc.) for the condition and some patients may not even consciously realize their blood sugar has dropped to dangerous levels. In addition to acquired tolerance, the use of alcohol and certain drugs (marijuana, for example) can create moderately similar symptoms to those of hypoglycemiaTemplate:Fact (especially when used in combination) and for this reason the patient may not realize he/she has contracted hypoglycemia.

Persistent elevations in blood sugar (and therefore HbA1c) increase the risk for the long-term vascular complications of diabetes such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor wound healing.

Lower than expected levels of HbA1c can be seen in people with shortened red blood cell life span, such as with glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red blood cell death. Conversely, higher than expected levels can be seen in people with a longer red blood cell life span, such as with Vitamin B12 or folate deficiency.

The approximate mapping between HbA1c values and average blood glucose measurements over the previous 4–12 weeks is given by the following equation:[18]

Mean Plasma Glucose (mg/dl) = [35.6 × HbA1c (%DCCT)] - 77.3
HbA1c Avg. Blood Sugar
DCCT
(%)
IFCC[13]
(mmol/mol)
(mmol/L) (mg/dL)
4 20 3.6 65
5 31 5.6 101
6 42 7.5 136
7 53 9.5 172
8 64 11.5 208
9 75 13.5 243
10 86 15.5 279
11 97 17.4 314
12 108 19.4 350
13 119 21.4 386
14 130 23.3 421

Indications and use

Glycosylated hemoglobin is recommended for both (a) checking blood sugar control in people who might be pre-diabetic and (b) monitoring blood sugar control in patients with more elevated levels, termed diabetes mellitus. For a single blood sample, it provides far more revealing information on glycemic behavior than a fasting blood sugar value. That being said, fasting blood sugar tests are crucial in making treatment decisions. The American Diabetes Association guidelines are similar to others in advising that the glycosylated hemoglobin test be performed at least two times a year in patients with diabetes who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients with diabetes whose therapy has changed or who are not meeting glycemic goals.[19]

Glycosylated hemoglobin measurement is not appropriate where there has been a change in diet or treatment within 6 weeks. Likewise the test assumes a normal red blood cell aging process and mix of hemoglobin subtypes (predominantly HbA in normal adults). Hence people with recent blood loss or hemolytic anemia, or genetic differences in the hemoglobin molecule (hemoglobinopathy) such as sickle-cell disease and other conditions are not suitable for this test. The alternative fructosamine test may be used in these circumstances and it similarly reflects an average of blood glucose levels over the preceding 2 to 3 weeks.

There is variation among laboratories and a lack of consensus on a diagnostic threshold for glycosolated hemoglobin. It bears noting that the International Expert Committee Report, drawn from the International Diabetes Federation (IDF), the European Association for the Study of diabetes (EASD), and the American Diabetes Association (ADA), suggests the A1c level of 6.5% as a diagnostic level.[20] The Committee Report further states that when A1C testing cannot be done, the fasting and glucose tolerance tests be done. Diagnosis of diabetes during pregnancy continues to require fasting and glucose tolerance measurements.

References

  1. Larsen ML, Hørder M, Mogensen EF (1990). "Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus". N. Engl. J. Med. 323 (15): 1021–5. PMID 2215560. 
  2. Huisman TH, Martis EA, Dozy A (1958). "Chromatography of hemoglobin types on carboxymethylcellulose". J. Lab. Clin. Med. 52 (2): 312–27. PMID 13564011. 
  3. Bookchin RM, Gallop PM (1968). "Structure of hemoglobin A1c: nature of the N-terminal beta chain blocking group". Biochem. Biophys. Res. Commun. 32 (1): 86–93. doi:10.1016/0006-291X(68)90430-0. PMID 4874776. 
  4. Rahbar S, Blumenfeld O, Ranney HM (1969). "Studies of an unusual hemoglobin in patients with diabetes mellitus". Biochem. Biophys. Res. Commun. 36 (5): 838–43. doi:10.1016/0006-291X(69)90685-8. PMID 5808299. 
  5. Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975). "Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c". Biochem. Biophys. Res. Commun. 67 (1): 103–9. doi:10.1016/0006-291X(75)90289-2. PMID 1201013. 
  6. Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976). "Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus". N. Engl. J. Med. 295 (8): 417–20. PMID 934240. 
  7. "Hemoglobin A1c Fact Sheet". Michigan Diabetes Research & Training Center. http://www.med.umich.edu/mdrtc/cores/ChemCore/hemoa1c.htm. Retrieved on 2007-12-26. 
  8. Developing Point of care HbA1c tests for Diabetes monitoring, Barry Plant, Originally Published IVDT July/August 2008
  9. Geistanger A, Arends S, Berding C, et al. (August 2008). "Statistical methods for monitoring the relationship between the IFCC reference measurement procedure for hemoglobin A1c and the designated comparison methods in the United States, Japan, and Sweden". Clin. Chem. 54 (8): 1379–85. doi:10.1373/clinchem.2008.103556. PMID 18539643. 
  10. Manley S, John WG, Marshall S (July 2004). "Introduction of IFCC reference method for calibration of HbA: implications for clinical care". Diabet. Med. 21 (7): 673–6. doi:10.1111/j.1464-5491.2004.01311.x. PMID 15209757. 
  11. "Standardisation of the reference method for the measurement of HbA1c to improve diabetes care" (PDF). The Association for Clinical Biochemistry and Diabetss UK. April 2008. http://www.acb.org.uk/docs/hba1c.pdf. Retrieved on 2009-07-02. 
  12. "All Change For HbA1c" (PDF). University Hospital of South Manchester. http://elearn-uhsm.co.uk/pathhandbook/Pathways_May_09.pdf. Retrieved on 2009-07-02. 
  13. 13.0 13.1 "HbA1c Standardisation For Laboratory Professionals" (PDF). Diabetes UK. http://www.diabetes.org.uk/upload/Professionals/Key%20leaflets/53130HbA1cLableaflet.pdf. Retrieved on 2009-07-02. 
  14. Rohlfing C, Wiedmeyer HM, Little R, et al. (2002). "Biological variation of glycohemoglobin". Clin. Chem. 48 (7): 1116–8. PMID 12089188. http://www.clinchem.org/cgi/content/full/48/7/1116. 
  15. "Hemoglobin A1c Test". MedicineNet.com. http://www.medicinenet.com/hemoglobin_a1c_test/article.htm. Retrieved on 2007-12-26. 
  16. "Executive Summary: Standards of medical care in diabetes—2009". Diabetes Care 32: S6–S12. 2009. doi:10.2337/dc09-S006. 
  17. Lehman R, Krumholz HM (2009). "Tight control of blood glucose in long standing type 2 diabetes". Brit Med J 338: b800. doi:10.1136/bmj.b800. 
  18. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE (February 2002). "Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial". Diabetes Care 25 (2): 275–8. PMID 11815495. http://care.diabetesjournals.org/content/25/2/275.long. 
  19. American Diabetes Association (2007). "Standards of medical care in diabetes--2007". Diabetes Care 30 (Suppl 1): S4–S41. doi:10.2337/dc07-S004. PMID 17192377. 
  20. The International Expert Committee (2009). "International expert committee report on the role of the A1C assay in the diagnosis of diabetes". Diabetes Care 32 (7). 

See also

External links

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